title: Modeling a methylmalonic acid-derived change point for serum vitamin B-12 for adults in NHANES.
abstract: BACKGROUND
  No consensus exists about which cutoff point should be applied for serum vitamin B-12 (SB-12) concentrations to define vitamin B-12 status in population-based research.
  
  
  OBJECTIVE
  The study's aim was to identify whether a change point exists at which the relation between plasma methylmalonic acid (MMA) and SB-12 changes slope to differentiate between inadequate and adequate vitamin B-12 status by using various statistical models.
  
  
  METHODS
  We used data on adults (≥19 y; n = 12,683) from NHANES 1999-2004-a nationally representative, cross-sectional survey. We evaluated 6 piece-wise polynomial and exponential decay models that used different control levels for known covariates.
  
  
  RESULTS
  The MMA-defined change point for SB-12 varied depending on the statistical model used. A linear-splines model was determined to best fit the data, as determined by the approximate permutation test; 3 slopes relating SB-12 and MMA and resulting in 2 change points and 3 subgroups were shown. The first group (SB-12 <126 pmol/L) was small and had the highest MMA concentration (median: 281 nmol/L; 95% CI: 245, 366 nmol/L; n = 157, 1.2%); many in this group could be considered at high risk of severe deficiency because combined abnormalities of MMA and homocysteine were very frequent and the concentrations themselves were significantly higher. The highest SB-12 group (SB-12 >287 pmol/L; n = 8569, 67.6%) likely had adequate vitamin B-12 status (median MMA: 120 nmol/L; 95% CI: 119, 125 nmol/L). The vitamin B-12 status of the sizable intermediate group (n = 3957, 33%) was difficult to interpret.
  
  
  CONCLUSIONS
  The 3 distinct slopes for the relation between SB-12 and MMA challenges the conventional use of one cutoff point for classifying vitamin B-12 status. In epidemiologic research, the use of one cutoff point would fail to separate the small, severely deficient group from the intermediate group that has neither normal nor clearly deficient vitamin B-12 concentrations (ie, unknown vitamin B-12 status). This intermediate group requires further characterization.
authors.affiliation: Office of Dietary Supplements, NIH, Bethesda, MD 20892-7517, USA. baileyr@mail.nih.gov
authors.forename: Regan L
authors.initials: RL
authors.lastname: Bailey
authors.forename: Ramon A
authors.initials: RA
authors.lastname: Durazo-Arvizu
authors.forename: Ralph
authors.initials: R
authors.lastname: Carmel
authors.forename: Ralph
authors.initials: R
authors.lastname: Green
authors.forename: Christine M
authors.initials: CM
authors.lastname: Pfeiffer
authors.forename: Christopher T
authors.initials: CT
authors.lastname: Sempos
authors.forename: Alicia
authors.initials: A
authors.lastname: Carriquiry
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Yetley
mesh_terms: D000328:Adult; D000368:Aged; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D016014:Linear Models; D008297:Male; D008764:Methylmalonic Acid / Q000097:blood*; D008875:Middle Aged; D009749:Nutrition Surveys; D009752:Nutritional Status; D012307:Risk Factors; D014805:Vitamin B 12 / Q000097:blood*; D014806:Vitamin B 12 Deficiency / Q000097:blood; D055815:Young Adult
chemical_list: D008764:Methylmalonic Acid; D014805:Vitamin B 12